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Harsh environment, severe aridity, and climate change create chronic water shortages in the Middle East. Technical challenges, socio-economic factors, and competing uses of water have escalated the difficulties in water planning at national and institutional levels. This research identifies opportunities and challenges associated with wastewater treatment systems and the potential for wastewater reuse in the West Bank, Tunisia, and Qatar through the following objectives: (1) identify the factors associated with successful and unsuccessful reuse schemes, (2) compare treated wastewater quality with end use application of treated wastewater, and (3) identify the governance and social challenges preventing the use of treated wastewater, specifically in agricultural applications. Water quality analyses and consultations with farmers, local stakeholders, and water and agriculture experts were conducted. Opportunities and challenges for treated wastewater reuse in agriculture are identified as the proximity of the treatment facility to agricultural areas, water quality, and motivation of farmers. With proper maintenance and appropriate monitoring, the modest (natural) treatment facilities in the West Bank and secondary treatment technologies in Tunisia are capable of producing effluent safe for use in production of certain agricultural products; however, in Qatar, despite massive investments in producing high-quality treated wastewater using advanced treatment technologies, there is little demand. Water policies, laws and acts, and action plans are urgently needed to be coupled and integrated for implementation.